Efficacy vs Placebo as Initial Combination Therapy With Pioglitazone

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Randomised, Double-blind, Placebo Controlled, Parallel Group 24 Week Study to Assess the Efficacy and Safety of BI 1356 (5 mg) in Combination With 30 mg Pioglitazone (Both Administered Orally Once Daily), Compared to 30 mg Pioglitazone Plus Placebo in Drug Naive or Previously Treated Type 2 Diabetic Patients With Insufficient Glycaemic Control.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00641043
• Other study ID #: 1218.15
• Secondary ID: 2007-002456-41
• Status: Completed
• Phase: Phase 3
• First received: February 29, 2008
• Last updated: January 22, 2014
• Start date: March 2008

Study information

• Verified date: January 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 ViennaGreece: National Organization fo Medicines (EOF) National Ethics CommitteHungary: National Institute of Pharmacy, H-1051 BudapestJapan: Ministry of Health, Labor and WelfarePortugal: INFARMED I.P.Romania: National Medicines Agency, BucharestSpain: AEMPSUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (Linagliptin) (5 mg / once daily) compared to placebo given for 24 weeks as initial combination therapy with pioglitazone 30 mg in patients with type 2 diabetes mellitus with insufficient glycaemic control.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 389
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria:

1. Signed and dated written Informed Consent (IC) by date of Visit 1a in accordance with Good Clinical Practice (GCP) and local legislation

2. Patients with a diagnosis of type 2 diabetes mellitus and treatment naive or previously treated with any oral hypoglycaemic agent; antidiabetic therapy has to be unchanged for ten weeks prior to informed consent.

3. Glycosylated haemoglobin A1 (HbA1c) 7.5-11% at Visit 2 (Start of Run-in).

4. Male and female patients aged > or = 18 and < or = to 80 years at Visit 1a (Screening).

5. Body Mass Index (BMI) < or = 40 kg/m2 at Visit 1a (Screening)

6. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.

Exclusion criteria:

1. Myocardial infarction, stroke or Transient Isquemic Atack (TIA) within 6 months prior to Inform Consent (IC)

2. Impaired hepatic function, defined by serum levels of either Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or alkaline phosphatase above 3 x upper limit of normal (ULN) determined at Visit 1a.

3. Known hypersensitivity or allergy to the investigational product or its excipients and/or to hydrochloride of pioglitazone or its excipients

4. Treatment with Glucagon-like peptide-1 (GLP-1) analogue / agonist within 3 months prior to IC.

5. Treatment with insulin within 3 months prior to IC

6. Treatment with anti-obesity drugs 3 months prior to IC.

7. Alcohol abuse within the 3 months prior to IC that would interfere with trial participation or drug abuse.

8. Participation in another trial with an investigational drug within 2 months prior to IC.

9. Fasting blood glucose > 240 mg/dl (=13.3 mmol/L) at screening (Visit 1).

10. Pre-menopausal women (last menstruation < or =1 year prior to signing IC) who:

• are nursing or pregnant,

• or are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner. No exception will be made.

11. Treatment with systemic steroids or change in the dosage of thyroid hormone within six weeks prior to IC

12. Heart failure New York Heart Asociation (NYHA) class I-IV, or history of heart failure.

13. Diabetic ketoacidosis within 6 months prior to IC.

14. Hemodialyzed patients due to limited experience with Thiazolidinediones (TZDs)

15. Any other clinical condition wich, in the opinion of the investigator, would not alow safe completion of the protocol and safe administration of BI1356 and pioglitazone.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• placebo + pioglitazone (30 mg)
placebo + overcapsulated 30 mg tablet, once daily
• Linagliptin + pioglitazone (30 mg)
5 mg tablet + overcapsulated 30 mg tablet, once daily

Locations

Country	Name	City	State
Austria	1218.15.43004 Boehringer Ingelheim Investigational Site	Feldkirch
Austria	1218.15.43001 Boehringer Ingelheim Investigational Site	Graz
Austria	1218.15.43003 Boehringer Ingelheim Investigational Site	Wien
Austria	1218.15.43005 Boehringer Ingelheim Investigational Site	Wien
Greece	1218.15.30004 Boehringer Ingelheim Investigational Site	Athens
Greece	1218.15.30007 Boehringer Ingelheim Investigational Site	Athens
Greece	1218.15.30017 Boehringer Ingelheim Investigational Site	Ioannina
Greece	1218.15.30002 Boehringer Ingelheim Investigational Site	Melissia-Athens
Greece	1218.15.30003 Boehringer Ingelheim Investigational Site	Nikaia
Greece	1218.15.30006 Boehringer Ingelheim Investigational Site	Thessaloniki
Greece	1218.15.30014 Boehringer Ingelheim Investigational Site	Thessaloniki
Greece	1218.15.30016 Boehringer Ingelheim Investigational Site	Thessaloniki
Hungary	1218.15.36003 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1218.15.36004 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1218.15.36006 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1218.15.36008 Boehringer Ingelheim Investigational Site	Debrecen
Hungary	1218.15.36005 Boehringer Ingelheim Investigational Site	Györ
Hungary	1218.15.36002 Boehringer Ingelheim Investigational Site	Szombathely
Japan	1218.15.81001 Boehringer Ingelheim Investigational Site	Amagasaki, Hyogo
Japan	1218.15.81005 Boehringer Ingelheim Investigational Site	Koganei, Tokyo
Japan	1218.15.81002 Boehringer Ingelheim Investigational Site	Osaka, Osaka
Japan	1218.15.81004 Boehringer Ingelheim Investigational Site	Shinjyuku-ku,Tokyo
Japan	1218.15.81003 Boehringer Ingelheim Investigational Site	Suita, Osaka,
Portugal	1218.15.35007 Boehringer Ingelheim Investigational Site	Aveiro
Portugal	1218.15.35001 Boehringer Ingelheim Investigational Site	Lisboa
Romania	1218.15.40504 Boehringer Ingelheim Investigational Site	Alba Iulia
Romania	1218.15.40501 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1218.15.40502 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1218.15.40503 Boehringer Ingelheim Investigational Site	Sibiu
Romania	1218.15.40505 Boehringer Ingelheim Investigational Site	Targu-Mures
Spain	1218.15.34002 Boehringer Ingelheim Investigational Site	Badalona
Spain	1218.15.34011 Boehringer Ingelheim Investigational Site	Badia del Vallés
Spain	1218.15.34001 Boehringer Ingelheim Investigational Site	Bercelona
Spain	1218.15.34012 Boehringer Ingelheim Investigational Site	Borges del Camp
Spain	1218.15.34013 Boehringer Ingelheim Investigational Site	Centelles
Spain	1218.15.34007 Boehringer Ingelheim Investigational Site	Granada
Spain	1218.15.34008 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat (Barcelona)
Spain	1218.15.34009 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat (Barcelona)
Spain	1218.15.34004 Boehringer Ingelheim Investigational Site	Madrid
Spain	1218.15.34006 Boehringer Ingelheim Investigational Site	Madrid
Spain	1218.15.34010 Boehringer Ingelheim Investigational Site	Sant Adrià del Besós (Barcelona)
Spain	1218.15.34005 Boehringer Ingelheim Investigational Site	Sevilla
Spain	1218.15.34014 Boehringer Ingelheim Investigational Site	Vic (Barcelona)

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Greece,  Hungary,  Japan,  Portugal,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c Change From Baseline to Week 24	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and week 24	No
Secondary	HbA1c Change From Baseline to Week 6	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and week 6	No
Secondary	HbA1c Change From Baseline to Week 12	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and week 12	No
Secondary	HbA1c Change From Baseline to Week 18	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and week 18	No
Secondary	FPG Change From Baseline to Week 24	This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.	Baseline and week 24	No
Secondary	FPG Change From Baseline to Week 6	This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.	Baseline and week 6	No
Secondary	FPG Change From Baseline to Week 12	This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.	Baseline and week 12	No
Secondary	FPG Change From Baseline to Week 18	This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetes medication.	Baseline and week 18	No
Secondary	Percentage of Patients With HbA1c <7.0% at Week 24	The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%. Only patients with baseline HbA1c >= 7%	Baseline and Week 24	No
Secondary	Percentage of Patients With HbA1c<7.0 at Week 24	The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.	Baseline and Week 24	No
Secondary	Percentage of Patients With HbA1c <6.5% at Week 24	The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%. Only patients with baseline HbA1c >= 6.5%	Baseline and Week 24	No
Secondary	Percentage of Patients With HbA1c<6.5% at Week 24	The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%	Baseline and week 24	No
Secondary	Percentage of Patients Who Have an HbA1c Lowering by 0.5% at Week 24	The percentage of patients with an HbA1c reduction from baseline greater than 0.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%.	Baseline and Week 24	No

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